Community-acquired pneumonia (CAP) is one of the most common pediatric infections, a major cause of morbidity in industrialized countries, and a leading cause of mortality worldwide in children under five years of age (Mulholland K, Lancet 2007; 370(9583): 285-9); Pio A, BWHO; 2003; 81(4):298-300). CAP may be caused by multiple agents alone or in combination, including respiratory viruses, Streptococcus pneumonia, Haemophilus influenzae, Chlamydia and Mycoplasma pneumoniae (Yin C C Respirology, 2003; 8(1):83-9; Chiang W C Respirology 2007; 12(2):254-61; Juven T PIDJ 2000; 19(4); 293-8). Etiological diagnosis is particularly challenging in young children, in whom blood cultures usually remain negative, bronchial secretions are rarely accessible, and frequent nasopharyngeal carriage limits the usefulness of microbial detection. Increasing the number of assays for pathogen detection nevertheless enhances the likelihood of the identification of a causal agent (Wang Pediatr Pulmonol 2008 February 43(2)150-9; Nakayama E J Infect Chemother 2007, 13(5):305-13), and recent studies using modern diagnostic tools have repeatedly identified S. pneumoniae as a leading cause of CAP, both in primary-care, and in hospital settings (Juven T PIDJ 2000; 19(4): 293-8; Michelow I C; Pediatrics 2004; 113(4):701-7).
Protection against pneumococcal infection is essentially mediated by antibodies promoting opsonophagocytosis. Such antibodies may be directed against pneumococcal polysaccharides (PPS) or pneumococcal surface proteins (PSP). In the absence of pneumococcal immunization, such antibodies are elicited by pneumococcal exposure, colonization and/or infections. The lack of protective antibodies against pneumococcal antigens is thus at the basis of the vulnerability of infants and young children to pneumococcal disease. Although certain PSPs have been used in the serological diagnosis of pneumococcal infections, with excellent specificities and positive predictive values, such studies have frequently been limited by a low sensitivity in children. This was largely attributed to higher colonization prevalence interfering with serological analyses (Scott, et al. Clin. Diagn. Lab. Immunol. 2005).
The etiological diagnosis of pneumococcal pneumonia remains challenging, particularly in young children. Microbial diagnosis based on blood culture or DNA amplification has a high specificity but a low sensitivity in children who are rarely bacteremic. In contrast, high rates of nasopharyngeal colonization limits the sensitivity of assays detecting bacteria and/of fragments thereof in nasopharynx or urine samples (Dowell, S. F., Clin. Infect. Dis. 2000 32:824-825). The quest for a robust methodology of serological diagnosis of pneumococcal pneumonia has been met with many difficulties (Kanclerski, J Clin Microbiol 988; Korppi M, Eur J Clin Microbiol Infect Dis 2007).
Diagnosis of community-acquired pneumonia (CAP) is particularly challenging in young children through traditional laboratory methods. There is a need in the field for reagents and methods useful for accurately and quickly diagnosing CAP, especially in young children. This need relates to both individual diagnosis, which requires assays providing rapid results with high sensitivities and negative predictive values to avoid useless antibiotic administration, and in epidemiological studies requiring assays with high specificity and positive predictive values for optimal case definition and adequate sensitivity to correctly estimate disease burden. Reagents and methods for accurately and quickly diagnosing CAP are described herein.